Initial PSA Oscillations Precede Prolonged Stable Disease in a Patient Treated With a Therapeutic Cancer Vaccine
2012
Prostate cancer is the second leading cause of death from cancer for men in the United States, claiming over 32,000 lives each year.1 Patients who present with bone metastasis have a 5-year survival rate of 3%.2 Metastatic prostate cancer is initially treated with either hormonal therapy or orchiectomy to deprive prostate cancer cells of testosterone, which binds to the androgen receptor and induces cellular proliferation. Although these treatments may initially limit tumor growth, the cancer cells will ultimately proliferate in spite of decreased levels of testosterone, a state known as castration resistance,3 increasing the potential for metastasis. Conventional treatment for metastatic castration-resistant prostate cancer (mCRPC) employs additional agents, such as androgen receptor antagonists (ARAs) and cytotoxic chemotherapy (i.e., docetaxel and cabazitaxel), which has been shown to prolong survival and palliate symptoms in patients with mCRPC.4
The recent approval by the U.S. Food and Drug Administration (FDA) of sipuleucel-T for mCRPC and ipilimumab for metastatic melanoma have generated significant momentum in the field of cancer immunotherapy. PSA-TRICOM (PROSTVAC®) is an investigational, off-the-shelf, vector-based therapeutic cancer vaccine genetically engineered with transgenes for prostate-specific antigen (PSA) and 3 human T-cell costimulatory molecules.5 A phase II randomized, placebo-controlled trial in 125 patients with mCRPC demonstrated a survival benefit of 8.5 months for patients treated with PSA-TRICOM compared to patients treated with placebo (25.1 vs. 16.6 months; P = 0.0061).6 In a separate single-arm study in 32 patients with mCRPC, the median overall survival was 26.6 months, and enhanced PSA-specific T-cell responses were associated with improved survival.7 The most common adverse event in these trials was a mild, local injection-site reaction, with only a subset of patients experiencing systemic flu-like symptoms. One patient had grade 3 injection-site cellulitis.6
Here we present a case report of a patient who, despite multiple negative prognostic factors, demonstrated prolonged survival with minimal toxicity after receiving treatment with PSA-TRICOM. Furthermore, the patient had a prolonged stable disease course while on PSA-TRICOM in spite of fluctuations in his PSA.
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